This invention relates to testing in the fields of chemistry, biology, and biotechnology. In particular, the invention relates to testing for pathogens and other analytes using a surface plasmon resonance (SPR) process.
Surface plasmon resonance (SPR) is a powerful analytical principle which is very sensitive to changes on an interrogated surface. Surface plasmons are generated in certain metals when light is incident upon the prism metal interface at a specific angle. As the properties of the surface change, e.g., the binding of a molecule to the surface, the angle at which SPR occurs is measurably shifted. The presence of a surface plasmon reduces the amount of light reflected at the specific angle, so a binding event on the surface results in a direct translation of the reflection minima: a parameter that is readily measurable.
In the background art, instruments utilizing SPR as a method of detection have been limited to laboratory use due to bulky size, limited field portability, and complicated operating procedures. Despite their shortcomings, SPR instruments are highly sensitive to extremely small changes at the interrogated surface. This makes the principle ideal for ultra-trace level detection. What is needed, however, is a compact detection system, with a simple user interface and operation, as well as pre-functionalized surfaces which together limit the required user skills to pressing buttons, performing simple sample injections upon prompting, and reading the result from a screen.
The Spreeta™ SPR transducer is an inexpensive SPR transducer that was originally developed by Texas Instruments, Inc. and is currently manufactured by Sensata Technologies, Inc. of Attleboro, Mass. The Spreeta™ SPR transducer has become competitive with other SPR methods and instruments, rivaling other SPR-based designs. The Spreeta™ SPR transducer contains a light source, prism, and a charge-coupled device (CCD) to generate light, interrogate the active surface at multiple angles, and recover the reflection signal of SPR respectively. Electronic circuitry drives the Spreeta™ SPR transducer, as well as extracts and analyzes the signal it produces to characterize the SPR result and determine whether a compound of interest is present. On the face of the Spreeta™ SPR transducer, a single use functionalized chip bears the plasmon-generating metal as the active, interrogated surface and the self-contained fluidics portion of a chip into which the sample is injected and retained.
The SPR technique is readily sensitive to mass changes well below the level of nanograms per milliliter without the benefit of secondary labeling techniques. The technique has the ability to use a mass-labeling technique for secondary amplification if necessary to provide additional signal under the condition of a positive binding event. For example, the system will recognize a bound virus, and generate an additional signaling event, allowing for greater sensitivity, improved likelihood of positive identification, and reduction of the lower detection limit.
Though SPR has been developed as a technology over the past 20 years, it is still being advanced through physical and computational means. Faster processing with modern hardware allows for a more compact electronics package, enabling portability, as well as faster sampling rates and resultant smoothness and reliability of signal.
In the physical interactions which take place on the active SPR surface, there are other advancements in the form of surface modification, perhaps most notably in the realm of nanoparticle labeling and nanotexturing of surfaces. This incorporation of nanotechnology with SPR is still in a very experimental state, but shows promise to improve the detection limits of the technique. SPR technology has largely been limited to laboratory use, where it provides high-sensitivity, high-specificity molecular identification and is utilized in sample testing for the presence of cells, viruses, biomolecules, nucleic acids and other compounds.
The background art is characterized by U.S. Pat. Nos. 3,656,833; 4,931,402; 5,156,976; 5,209,904; 5,607,643; 5,912,456; 6,432,364; 6,611,367; 6,756,223; 6,870,627; 6,956,695; 7,307,730; 7,333,197; 7,554,657; 7,738,934; 7,842,242; and 7,842,247; and U.S. Patent Application Nos. 2003/0003018; 2003/0206708; 2006/0188401; 2007/0222998; 2007/0279634; 2009/0103099; 2009/0303489; 2010/0096561; 2010/0103421; 2010/0150781; 2010/0216975; and 2010/0284012; the disclosures of which patents and patent applications are incorporated by reference as if fully set forth herein. The background art is also characterized by the following patents and patent applications: TW 249768; WO 2008/007115; and WO/2009/022985.